Recent patent on combination of antagonists of dopamine receptors, glycolysis inhibitor, and a cholesterol lowering agent to inhibit the growth of pancreatic cancer
The patent application was done by two important institutions active in the field of cancer research:
Deutsches Krebsforschungszentrum Stiftung des Öffentlichen Rechts (Heidelberg, DE)
The Royal Institution for the Advancement of Learning/McGill University (Montreal, CA)
The patent suggests that the combination of
- dopamine receptor antagonists D2 (DRD2) such as pimozide, haloperidol,
- glycolisis (fermentation) inhibitors such as 2DG or 3BP and
- cholesterol inhibitors such as Atorvastatin
The concept is the following:
- Treatment with antipsychotic drugs, such as pimozide or haloperidol, induce ER-stress.
- ER stress triggers a gene regulatory program, which is characterized by overexpression of genes encoding enzymes involved in glycolysis and lipogenesis
- Therefore, this leads to glycolytic activity as well as increased phospholipid turnover and cholesterol levels in cancer cells under ER-stress conditions
- Specifically, glycolysis and cholesterol biosynthesis pathways, which are activated by DRD2 antagonists, are used by cancer cells to survive the excessive ER stress induced by DRD2 antagonists
- As a result, combination of dopamine receptor antagonists D2 (DRD2), with glycolisis inhibitor 2DG and cholesterol biosynthesis inhibitor Atorvastatin reduced tumor development.
So the key anti-cancer mechanisms here is the ER-stress. Actually, 2DG also induces ER stress.
Note that the ER-stress-driven glycolysis and alterations in cholesterol homeostasis have been linked to chemoresistance in cancer cells
Combined therapeutic approach for pimozide, gemcitabine, 2-DG and Atorvastin resulted in complete arrest of tumor growth.
Here is the patent http://www.freepatentsonline.com/y2020/0030356.html
I previously discussed the glycolisis inhibitor 2DG here https://www.cancertreatmentsresearch.com/2-deoxyglucose-2-dg/ but if this is used in order to be effective it has to be taken metronomic https://www.cancertreatmentsresearch.com/a-new-approach-to-improve-effectiveness-of-cancer-therapies-is-getting-ready-to-begin-human-trials/
Other glycolisis inhibitors were discussed here https://www.cancertreatmentsresearch.com/drugs-and-supplements-that-block-fermentation-and-help-fight-cancer/
Statins such as Atorvastatin were discussed here https://www.cancertreatmentsresearch.com/cholesterol-lowering-statin-drugs-to-fight-cancer/